Serum markers of intestinal and blood-brain barrier permeability (zonulin and claudin-5) in patients with Parkinson’s disease

Objective. This study aimed to assess serum concentrations of intestinal and blood-brain barrier permeability markers, specifically zonulin and claudin-5, in patients with Parkinson’s disease (PD) and in those with stage one and two dyscirculatory encephalopathy (DE). The study also evaluated the relationship between these marker levels and the clinical features of the diseases. Material and methods. This cross-sectional comparative study included 146 patients (116 with PD and 30 with DE). Serum levels of zonulin and claudin-5 peptides were measured using enzyme-linked immunosorbent assay. Copy number variations in the SNCA, Parkin, UCHL1, PINK1, DJ1, LRRK2, and ATP13A2 genes were analyzed by multiplex ligation-dependent probe amplification (MLPA), while GBA1 variants were assessed by polymerase chain reaction (PCR). Results. Claudin-5 levels were significantly higher in patients with PD compared to the control group: 2.5 [1.3; 3.8] ng/mL in patients with PD versus 1.0 [0.3; 2.5] ng/mL in patients with DE (p=0.001). Zonulin levels were also higher in patients with PD than in the DE group, at 48.0 [34.5; 59.8] ng/mL versus 40.1 [21.7; 55.0] ng/mL, respectively. Zonulin concentration showed a positive correlation with MMSE scores (ρ=0.20; p<0.0001) and MoCA scores (ρ=0.19; p<0.0001). Zonulin levels were inversely correlated with the score on the third part of the MDS-UPDRS scale (ρ=–0.18; p<0.0001). Claudin-5 levels were highest in patients with early-stage PD (2.6 [1.8; 4.2] ng/mL), compared with 2.3 [1.0; 3.7] ng/mL in advanced-stage PD and 1.0 [0.3; 2.5] ng/mL in patients with DE (p=0.001). Pairwise comparisons revealed a statistically significant difference between the early-stage PD subgroup and the DE group. Similarly, patients with early-stage PD had the highest median zonulin concentration (51.8 [41.3; 58.4] ng/mL), compared with 40.0 [32.0; 59.8] ng/mL in the advanced group and 40.1 [21.7; 55.0] ng/mL in patients with DE (p=0.041). In the main group, mutations in PD-associated genes were identified in 32 patients. Claudin-5 levels were higher in patients with PD than in the DE group for both genetic and sporadic forms (p=0.004). Claudin-5 levels did not differ significantly between genetic and sporadic forms of PD (p=0.824). Zonulin levels were significantly higher in patients with genetic forms of PD compared to both sporadic forms (p=0.007) and the DE group (p=0.006). Sporadic forms of PD did not differ significantly from the comparison group in zonulin levels (p=0.746). Overall, intergroup differences in zonulin were statistically significant (p=0.001). Conclusion. Assessing specific changes in intestinal and blood-brain barrier permeability markers in patients with PD is a significant area of research for understanding the disease’s pathogenesis. Further investigation is necessary to predict disease progression and to identify potential targets for pathogenetic therapy.